By Tim Batchelder for Townsend Letter for Doctors and Patients

Obesity and diabetes are two of the most prevalent health conditions in industrial nations. Yet, despite billions of dollars in research and countless diets, drugs and therapies, rates of these disorders continue to soar. Perhaps what is needed is not more investigation into the molecular basis of these disorders but greater attention to the environmental conditions that allow expression of them. This is precisely the tact taken by evolutionary biologists and anthropologists who study health.

From this perspective our craving for fat and sugar and desire for sedentary lifestyles are natural: in our evolutionary environment it was precisely these factors that were most rare. The solution, then, to these diseases of civilization is to recreate this evolutionary environment to the greatest extent possible, an approach that can be called "culture engineering" to match the emphasis on genetic engineering found today.

Oversensitive Insulin Triggers

One of the early pioneers in the application of genetic knowledge to understanding health conditions was James Neel. In 1962 he published the novel suggestion that the basic defect in type II or non-insulin-dependent diabetes mellitus (NIDDM) was a quick insulin trigger. This means that the pancreas secretes insulin too quickly in response to elevated blood sugar and was an asset to our tribal, hunter-gatherer ancestors with their intermittent, sometimes feast-or-famine alimentation, since it should have minimized renal loss of precious glucose. This quick insulin trigger was under genetic control. Since too quick an insulin trigger might be as disadvantageous as one that is too slow, it was suggested that this genetic control might take the form of a balanced polymorphism, by analogy with the polymorphisms for the sickle cell allele (S) then receiving so much attention. Recently, two other conditions: essential hypertension and obesity, have emerged as epidemiologically similar to NIDDM, being diseases of civilization with gradual onset that have inherited, familial characteristics.

Fieldwork in Amazonia and Mexico

Neel decided to see whether there was a predisposition to NIDDM in some tribal groups that surfaced with reservation-style living. He performed glucose tolerance and other tests on two groups of unacculturated Amerindians, the Yanomama and Mambo of the Brazilian Amazon Basin. Plasma glucose, insulin, pancreatic polypeptide, and growth hormone responses differed somewhat among the two groups but neither of them showed the large glucose intolerance of the highly acculturated and very obese adult North American Pima.

To validate Neel's findings authors of another recent study (Valencia et al 1999) examined NIDDM in Pima Indians of southern Arizona and the Pima Indians of the Sierra Madre Mountains of northern Mexico. The Pima Indians are descendents of the Hohokam group that settled in the valleys of the Gila and Salt rivers in Arizona about 2,000 years ago. At that time, they used sophisticated agricultural and irrigation systems together with hunting and gathering to supplement their diet. At the end of the 19th century, non-Hispanic immigrants diverted their water supply and, consequently, disrupted their traditional forms of agriculture which led to many health problems. Government assistance programs and a cash economy replaced traditional farming activities for the Arizona Pimas. The Arizona Pimas now have the highest reported prevalence worldwide of type 2 diabetes, as well as considerable obesity and other chronic diseases.

In contrast to the Arizona Pimas, Mexican Pima living in the Sierra Madre mountains live at 1600 m above sea level and practice traditional, non-mechanized agriculture. They cultivate corn, beans (Phaseolus vulgaris), and potatoes as their main staples plus a limited amount of seasonal vegetables and fruits such as zucchini squash, tomatoes, garlic, green pepper, peaches and apples. They also make heavy use of wild and medicinal plants in their diet. Their crops are planted on sloped fields called "maguechis," which are very labor intensive. They also participate in lumber milling, which is also non-mechanized. There is no electricity or running water in their homes, and they have to walk long distances to bring in drinking water or to wash their clothes. They use no modern household devices; consequently, food preparation and household chores require extra effort by the women. Based on linguistic similarities it is estimated that the two Pima groups separated 700 to 1000 years ago.

To study the impact of environmental and genetic factors on the prevalence of type 2 diabetes and obesity, the researchers compared 226 Mexican Pimas (120 males and 106 females) with 984 Pimas (406 males and 578 females) from the Gila River community in Arizona. A group of 198 unrelated non-Pima individuals (104 males and 94 females) living in the same environment as the Mexican Pimas were also included in the study.

Obesity (BMI of 30 or above) was present in only 13% of the Mexican Pimas and 19% of the non-Pima Mexicans, whereas 69% of the Arizona Pimas met the criterion for obesity. The average difference in body weight between the Arizona and Mexican Pima men and women was close to 30 kg.

Physical activity was estimated by the methodology of Kriska et al., which includes a questionnaire that accounts for the time spent on various leisure and occupational activities. Mexican Pimas and non-Mexican Pimas had 23 and 26 hours per week (in the past year) of occupational physical activity, respectively, whereas Arizona Pimas had less than 5 hours.

The principal occupational categories for Mexican Pimas included homemaking, wood milling, nonmechanical farming, and livestock breeding, as well as complementary activities such as security, construction, and mining. The principal activities of the Arizona Pimas included homemaking, mechanical farming, construction, landscape work, equipment or vehicle operation, and such other activities as security, maintenance, hair styling, fire fighting, and clerical work.

Diet studies, using the 24-hour recall method, indicated a fat intake of 26% of total energy intake for the Mexican Pimas, 25% for the non-Pima Mexicans, and 35% for the Arizona Pimas. Cholesterol intake was 211 mg/day for the Mexican Pimas, 255 mg/day for the non-Pima Mexicans, and 471 mg/day for the Arizona Pimas. The polyunsaturated to saturated fat ratios were 1. 1, 0.9, and 0.5 for the same groups, respectively. Dietary fiber intake was 53 g/day for both Mexican groups and 19 g/day for the Arizona Pimas.

In sum, the two Mexican groups lived in an environment which put them at much lower risk for diabetes and obesity despite a high genetic susceptibility. In contrast, the Arizona Pima suffer from extremely high rates of these disorders due to their non-traditional lifestyle.

Laboratory Studies

Based on these field studies scientists have been busy looking for the "diabetes gene" or a single major locus that causes NIDDM. Bogardus and Knowler report that in the Pima Indians, fasting insulin levels yielded evidence for the action of a single major gene. Mitchell reports that a major (dominant) allele controls insulin levels during insulin challenge tests in Mexican Americans and this allele accounts for 35% of changes in 2-hour insulin levels. Recently the entire human genome was searched for key genes in Mexican Americans with NIDDM and led to the discovery of a susceptibility locus on chromosome 2, an allele that accounts for 30% of familial clustering of the disorder.

These studies all fit together nicely with earlier fieldwork on the Pima when one considers that 31% of Mexican American genes are descended from Amerindians. Interestingly, unlike Mexican Americans, smaller samples of non-Hispanic whites and Japanese show no major locus for NIDDM susceptibility on chromosome 2. Schermacher analyzed Caucasian families with NIDDM and found a recessive allele controlling fasting insulin levels that causes about 33% of the difference in fasting insulin levels in this population.
One stumbling block to a genetic understanding of NIDDM is its supposed "adult onset". However, studies have shown that children age 1-9 either of whose parents have NIDDM have abnormal glucose tolerance tests. Children age 5-19 with NIDDM parents also show higher fasting and 2-hour blood insulin levels. They also tend to be obese. All of these factors are predictors of future NIDDM.

Syndrome X

It's hard not to be excited by Syndrome X if you are even remotely interested in evolutionary biology, anthropology and health. Syndrome X is the combination of NIDDM, hypertension, and a truncal/abdominal (android) obesity and has also been called insulin resistance syndrome or the deadly quartet.

To find out whether this syndrome was in fact the ultimate example of the thrifty genotype in action, Neel took a look at levels of obesity, hypertension, NIDDM, and combinations of them, in two adult populations in the United States and in Japan. He found that there were many females in particular showing the triad. However, he noted that obesity and hypertension were more closely associated than obesity and NIDDM. He suggests that Syndrome X is thus not a true syndrome whose elements share a common (genetic) pathophysiology.

Body Composition in the Stone Age

One of most interesting recent discoveries in evolutionary medicine is the radical difference in body composition and lifestyles of Stone Age versus industrial people. Eaton notes that alimentation was intermittent in Stone Age humans versus the almost constant consumption of modern industrial humans. He also notes that while trained athletes have more muscle mass than early man modern man has much more fat between muscles, called sarcopenia. Fat and skeletal muscle cells have very different insulin sensitivities which means that the sensitivity to insulin of skeletal muscle has been radically changed in the transition to a technological society. This change wasn't accomplished by an increase in food calories as much as change in the type of calories consumed and decreased physical activity.

Total daily energy expenditure in adult members of hunter-gatherer and traditional agricultural societies is about 3000 kcal/day compared to 2000 or less at present in industrial societies. In particular, modern industrial use of highly refined carbohydrates, with the resulting almost instantaneous "sugar highs," has altered our body's blood sugar balancing mechanisms drastically. This I might add is a major flaw in the various high protein, low carbohydrate diets being suggested at present: Stone Age humans did not consume large amounts of wild animal food, but rather primarily foraged for plant foods. The difference is not in protein intake (which is more than adequate in modern industrial diets) but rather the form and type of carbohydrate being consumed: refined, domesticated plant based versus complex, high fiber, wild plant based. There has been a parallel genetic evolution in the plant kingdom to match our dietary habits.

Hypertension and Obesity

Hypertension and obesity like NIDDM are diseases of civilization whose prevalence has skyrocketed with industrialization and are not usually found in hunter gatherers and low energy agriculturalists. The prevalence of hypertension and obesity in the U.S. is now 40% of adults. While some monogenically inherited forms of hypertension and obesity are known they are primarily multifactorial or polygenic. As with NIDDM a good indicator that these are genetic conditions is the occurrence of minor abnormalities early in life. Offspring of hypertensives show borderline hypertension and abnormal red blood cell sodium markers. Likewise, chubby children tend to become obese adults. Babies of overweight mothers often show aggressive feeding style.

Civilization Syndromes

While Neel prefers to avoid the Syndrome X term since these three diseases are not absolutely related by the same genetic mechanism, he does favor the creation of a term for a series of syndromes all related to the thrifty genotype concept. In particular he suggests the terms "syndromes of impaired genetic homeostasis" or "civilization syndromes," or the "altered lifestyle syndromes," to which other diseases may yet be added.

Culture Engineering

Since obesity is closely correlated with NIDDM and essential hypertension these two diseases will increase in prevalence as obesity increases. Neel notes that computer games designed specifically to appeal to kids and great amounts of TV watching are certain to accelerate the rates of obesity in children, unless a return to a simpler lifestyle can be accomplished.

Gene therapies such as adjusting the body's production of the hormone leptin are being investigated. However, Neel points out that we should be humble in our expectations for gene therapy. The monogenic disorders for which genetic therapy is feasible represent defects in a well understood metabolic cascade. By contrast, the multifactorial "diseases of civilization" represent perturbations of complex systems.

A much more promising and cost-effective approach to these conditions is what Neel has termed "culture engineering" to counterbalance the recent emphasis on genetic engineering. Just as genetic engineering implies a conscious effort to improve the genome, culture engineering implies a conscious effort to develop in all dimensions the environment in which the human genome finds its optimal expression. Eaton et al. have called this the Paleolithic Prescription and it constitutes a "return," where feasible, to aspects of a Paleolithic lifestyle, especially those involving diet and physical activity. Eaton and colleagues suggest much higher dietary fiber content and decrease in refined carbohydrate foodstuffs, less saturated fat, decreased sodium intake, and increased intake of micronutrients, either through an increased intake of fruits and vegetables or dietary supplementation.

Simultaneously, a return to a much higher level of physical activity must be started. In fact, exercise will most likely be the foundation of evolutionary approaches to wellness. Previous studies have shown that in most affluent societies one can get people to do heavy exercise if it is considered a recreational activity, whereas people will reject fasting or underfeeding.

Conclusions

Neel advocates for a government based national Paleolithic Prescription health education campaign that targets both children and adults. However, I am less certain this is the answer. By consistently prioritizing genetic engineering and other molecular techniques over cultural engineering the government has shown it has little interest in cultural and environmental solutions to our health problems. Fortunately, change might be much simpler. Though Neel never discusses it, thousands of people in the U.S. and other industrialized nations are already staging just such a return. The natural health and environmental movements have spawned such philosophies as voluntary simplicity and bio-regionalism which involve recreating a simpler, and evolutionarily more appropriate, lifestyle.

About the Author

Tim Batchelder is a science writer specializing in medical anthropology and human ecology topics. He has a B.A. from Hamilton College in linguistic anthropology and is pursuing further graduate coursework in human biology, ethnobotany, and ethnomedicine. He can be reached at timbatchelder@altavista.com.